T lymphocytes recognize antigen in the context of major histocompatibility complex (MHC) molecules. This recognition is mediated by the T cell receptor (TCR) alpha beta heterodimer. CD4 and CD8 molecules participate in this interaction either by increasing cellular adhesion and/or transmembrane signalling. The CD4 molecule is involved in recognition of the MHC class II proteins while the CD8 molecule is involved in MHC class I recognition. Here, we identified CD4-8- peripheral blood T cells that recognize the CD1 molecule, a class I like molecule that is not encoded in the MHC. Three D1 proteins (CD1a-c) consist of distinct heavy chains associated with beta 2 microglobulin. Some or all of these molecules are expressed on developing thymocytes, activated B cells and Langerhans cells. We propose to generate a panel of CD4-8- T cells from normals and from patients with systemic lupus erythematosus, and characterize their recognition of CD1 on different target cells including CD1 transfectants. Antigen-specific CD1- restricted T cell clones will be generated using CD1+ antigen presenting cells (B cells and Langerhans cells). To directly demonstrate that the TCR recognizes CD1 we will colon and transfect the TCR alpha and beta genes from a CD1a-specific T cell to confer CD1 specificity to a recipient cell. These experiments may show that in addition of MHC class I and II antigens, T lymphocytes (particularly those which are CD-8-) can recognize antigens presented by CD1 molecule. In addition to the known TCR dimers, alpha beta and gamma delta, we have found the TCR beta delta heterodimer expressed on a T leukemia cell line. We propose to examine the occurrence of this new TCR heterodimer in the thymus, the periphery, and in malignancies in man. The pairing of TCR beta and TCR delta raises important questions not only regarding TCR expression in development, but also what effect this combinatorial association might have on the T cell repertoire. These experiments address a putative new antigen-presenting molecule (CDI) and a previously unrecognized TCR heterodimer (beta delta). Such studies may provide information on novel aspects of T lymphocyte recognition and immune responses.